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Novel cancer‐oocyte biomarker SAS1B as a potential target in head and neck squamous cell carcinoma (HNSCC)
Author(s) -
Lee Christina Ju,
AndersonKnapp Kiley,
Pires Eusebio,
Jameson Mark,
Herr John
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1107.1
Subject(s) - head and neck squamous cell carcinoma , cancer , cancer research , biomarker , biology , cd44 , head and neck cancer , oncology , medicine , cell , biochemistry , genetics
Head and neck squamous cell carcinoma (HNSCC) is the most common cancer of the head and neck region with a low overall 5‐year survival rate of 50%, highlighting the need for more effective therapeutics. A novel cancer‐oocyte biomarker, SAS1B ( s perm a crosomal S LLP1 b inding protein), presents substantial opportunities for development of novel diagnostics and therapeutics for patients with HNSCC. SAS1B has been recently discovered as a membrane‐associated zinc metalloprotease expressed in growing oocytes housed in the secondary follicle stage through ovulation, and is virtually absent in other tissues. SAS1B has been identified in approximately 77% uterine tumors including 74% endometrioid and 87% malignant mixed Mullerian tumors (MMMT). Given the range of cancers expressing SAS1B, probing for SAS1B gene and protein may increase the number of possible cancer patients in which a therapeutic method targeting SAS1B would potentially be beneficial. Twenty‐four primary human tumor specimens and eight HNSCC human‐derived cell lines were analyzed for ASTL message and SAS1B protein. A PCR assay unique to ASTL/SAS1B, excluding all of the other 134 human metalloproteases, has been developed with validated primers to amplify various domains of ASTL/SAS1B transcripts. SAS1B was identified in all samples of cell lines and primary tumors [100% incidence] using primers spanning a part of the c‐terminus of SAS1B. In addition, 46kDa and 65kDa SAS1B isoforms have been identified by Western blot using anti‐SAS1B polyclonal antibodies. To test the possibility of SAS1B as an immunotherapeutic target for HNSCC, live cell staining of an HNSCC cell line, OSC19 was carried out using indirect immunofluorescence with anti‐SAS1B polyclonal antibodies revealing cell surface localization of SAS1B. Future experiments will focus on in‐vitro cell killing assays using a duocarmycin‐conjugated antibody to test internalization of the antibody drug conjugate and subsequent growth arrest capabilities. The restricted localization of SAS1B presents opportunities for development of novel diagnostics and highly selective treatment approaches that spare both normal tissues and the ovarian reserve, thus potentially preventing unwanted negative side effects common in currently available therapeutics. Support or Funding Information n/A